Mechanical power normalized to lung-thorax compliance indicates weaning readiness in prolonged ventilated patients

Since critical respiratory muscle workload is a significant determinant of weaning failure, applied mechanical power (MP) during artificial ventilation may serve for readiness testing before proceeding on a spontaneous breathing trial (SBT). Secondary analysis of a prospective, observational study in 130 prolonged ventilated, tracheotomized patients. Calculated MP’s predictive SBT outcome performance was determined using the area under receiver operating characteristic curve (AUROC), measures derived from k-fold cross-validation (likelihood ratios, Matthew's correlation coefficient [MCC]), and a multivariable binary logistic regression model. Thirty (23.1%) patients failed the SBT, with absolute MP presenting poor discriminatory ability (MCC 0.26; AUROC 0.68, 95%CI [0.59‒0.75], p = 0.002), considerably improved when normalized to lung-thorax compliance (LTCdyn-MP, MCC 0.37; AUROC 0.76, 95%CI [0.68‒0.83], p < 0.001) and mechanical ventilation PaCO2 (so-called power index of the respiratory system [PIrs]: MCC 0.42; AUROC 0.81 [0.73‒0.87], p < 0.001). In the logistic regression analysis, PIrs (OR 1.48 per 1000 cmH2O2/min, 95%CI [1.24‒1.76], p < 0.001) and its components LTCdyn-MP (1.25 per 1000 cmH2O2/min, [1.06‒1.46], p < 0.001) and mechanical ventilation PaCO2 (1.17 [1.06‒1.28], p < 0.001) were independently related to SBT failure. MP normalized to respiratory system compliance may help identify prolonged mechanically ventilated patients ready for spontaneous breathing.


Definitions of ventilator variables and mechanical power indices Ventilatory ratio (VR)
Ventilatory ratio (VR) is a surrogate of pulmonary dead space fraction and a simple bedside index of impaired efficiency of ventilation 1-2 :

VR = VEmeasured * PaCO2-measured / VEpredicted * PaCO2-ideal
VEmeasured is the measured minute ventilation (mL/min), PaCO2-measured is the measured arterial pressure of carbon dioxide (mmHg), VEpredicted is the predicted minute ventilation calculated as predicted bodyweight x 1000 (mL/min), and PaCO2ideal is the expected arterial pressure of carbon dioxide in normal lungs if ventilated with the predicted minute ventilation. PaCO2-ideal is set at 37.5 mmHg (5 kPa) for all patients. VR is a unitless ratio, and a value approximating one would represent normal ventilating lungs.

Mechanical power normalized to dynamic lung-thorax compliance (LTCdyn-MP)
MP normalized to dynamic lung-thorax compliance (LTCdyn-MP) was calculated using MP and dynamic lung-thorax compliance (LTCdyn) 7 : This formula accounts for different effects of changes in respiratory rate, inspiratory pressure (Pmax), and PEEP (and thus changes in ∆Paw) on delivered energy. Increasing RR leads to a linear rise in energy transfer while increasing pressure (concomitantly increasing tidal volume) results in an exponential increment in power 3 .

Mechanical power normalized to dynamic lung compliance (Clung-MP)
Introducing esophageal pressure (Pes) to the formula for LTCdyn-MP, thereby replacing Pmax by absolute end-inspiratory transpulmonary pressure (PL_end-insp) and ∆Paw by the transpulmonary driving pressure (∆PL), leads to an equation that estimates stress intensity to the lungs in the pressure-controlled ventilation mode (Clung-MP):

ROC curve analysis
To assess the accuracy of the variables analyzed to predict weaning outcome, a receiver operating characteristic (ROC) curve analysis was performed in the entire study population (Fig. S1), and diagnostic performance was expressed as the area under the ROC curve (AUROC). Furthermore, we compared ROC curves of different prediction variables.

k-fold cross-validation
To ensure that the proportion of patients with successful and unsuccessful weaning in both groups reflected the ratio in the whole study population (stratification of outcome), patients were randomly assigned to one of two groups in a stratified, two times repeated, 2-fold cross-validation 8 (groups A/B or C/D) (Fig. S1). Each of the two groups then acted once as a training set and once as a test set. Threshold values that best predicted prolonged weaning failure were derived from the training sets using ROC curve analysis employing the non-parametric method from DeLong 9 . The thresholds that minimized the difference between sensitivity and specificity (assuming equal clinical implications from a false positive and a false negative test) were then used in the test sets to determine the diagnostic performance of each variable. The resulting cross-validated performance of each index, expressed as sensitivity (Sens), specificity (Spec), positive predictive value (PPV), negative predictive value (NPV), accuracy (ACC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) 10 , F1 score, and Matthews correlation coefficient (MCC) 12 , equals to the averaged metrics derived from all (four) test sets (Fig. S1, Fig. S2).

Legend
Categorical variables are presented as numbers (%). *: ABG at the end of the SBT was missing in seven patients due to severe respiratory distress, requiring immediate resumption of mechanical ventilation Abbreviations: SBT, spontaneous breathing trial; bpm, beats per minute. Legend > / ≤ indicate whether values above/below the threshold value predicted failure of the SBT. The associated criterion is the threshold value that minimized the difference between sensitivity and specificity of the test, graphically corresponding to the intersection of the line connecting the left-upper corner and the right-lower corner of the unit square and the ROC curve.

Legend
The correlation of each variable in the whole study population with the duration of the first SBT presented as Pearson's r (with 95% confidence intervals).